Ex Vivo Analysis of Kidney Graft Viability Using 31P Magnetic Resonance Imaging Spectroscopy

Abstract

Background. The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. 31P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. Methods. To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. Results. Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. Conclusions. ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient’s survival.

Renal Normothermic Machine Perfusion: The Road Toward Clinical Implementation of a Promising Pretransplant Organ Assessment Tool

“…A second tool to advance pretransplant kidney viability assessment during NMP is through innovative imaging methods. 11,[135][136][137] Near-infrared spectroscopy, (functional) MRI ([f]MRI), positron emission tomography, contrast-enhanced ultrasound, ultrafast ultrasound imaging, laser speckle imaging, and multiphoton microscopy imaging all have the potential to unravel renal physiological processes during NMP in a noninvasive manner (Table 3). Additionally, these methods may provide more information about regional differences in the functional properties of the ex vivo perfused kidney.…”

A Review of Current and Emerging Trends in Donor Graft-Quality Assessment Techniques

“…Moreover, they found that ATP levels and cortical and medullary gadolinium elimination were inversely correlated with the severity of kidney histological injury. Thus, the measured parameters may be considered as biomarkers of kidney injury after warm ischemia, and Longchamp et al's method provides an innovative non-invasive approach to assessing kidney viability prior to transplantation [118].…”

Sense and Sensibilities of Organ Perfusion as a Kidney and Liver Viability Assessment Platform

“…Various molecular mechanisms are active in ischemia reperfusion injury. There is the critical role of the anaerobic metabolism during ischemia, resulting in intracellular acidosis, ATP depletion, and failure of ion-exchange channels, setting the stage for reperfusion injury ( 15 ). Post-reperfusion, innate and adaptive immune responses are activated by reactive oxygen species and damage associated molecular patterns, resulting in a sterile inflammation ( 16 – 19 ).…”